2016-07-16.log

--- Log opened Sat Jul 16 00:00:58 2016
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kanzurehmph07:52
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kanzurefenn: why bother with sequencing with FISSEQ and proten expression labeling stuff, if you are already placing the tissue slice in front of a microscope anyway? you might as well do imaging, not sequencing.08:27
kanzurefor connections i think sequencing is still required.08:27
kanzurehttps://openaps.org/ "open artificial pancreas project"08:29
kanzurehttps://openaps.org/reference-design/08:29
kanzurehttps://github.com/openaps/openaps08:29
kanzurehttps://github.com/openaps/oref008:30
CaptHindsightI'm glad they chose the pancreas, the pancreas and the spleen tend to get overshadowed by other organs in the press08:53
CaptHindsighthow many news articles feature the spleen? It tends to be heart, lungs and stomach08:54
kanzure.wik systematic evolution of ligands by exponential enrichment08:56
yoleaux"Systematic evolution of ligands by exponential enrichment (SELEX), also referred to as in vitro selection or in vitro evolution, is a combinatorial chemistry technique in molecular biology for producing oligonucleotides of either single-stranded DNA or RNA that specifically bind to a target ligand or ligands." — https://en.wikipedia.org/wiki/Systematic_evolution_of_ligands_by_exponential_enrichment08:56
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streetyI thought that open pancreas project was started and run by diabetics - i.e. they're building a device they themselves want to use / are using09:09
kanzurehere is a good overview of SELEX things http://www.medicinal-chemistry.org/files/harki/The%20Discovery%20of%20Protein-Targeting%20Aptamers%20by%20SELEX.pdf09:11
kanzure"cell-SELEX" i wonder if this is for cell surface property selection, or if this is something else..09:13
kanzureanother overview http://www.trilinkbiotech.com/tech/selex.asp09:17
kanzurepeptide sequencing still works, right? we could modify a ribosome to print random amino acid chains instead of looking at RNA.  the goal would be to select for ribosomes that print really long proteins. and then later the goal would be to select for ribosomes that are more controllable by human influence or human-generated signals. (this is an alternative to the idea of using a library of 64 synthetases and an evolved ribosome that binds ...09:21
kanzure... to whatever synthetase we give it).09:21
CaptHindsightkanzure: for some reason the inkjet DNA printer is suddenly getting interest yet the paper is from 200409:23
kanzurehttps://www.google.com/search?q=site%3Aigem.org+SELEX09:24
kanzureCaptHindsight: POSAM? yeah i think it has always been popular :).09:24
CaptHindsightkanzure: maybe in here but not outside09:24
CaptHindsightthe ChinaCo flatbad inkjets are made too crappy, like most reprap style printers...09:25
CaptHindsightso I can't start with those and expand, cheap bastards09:26
kanzurethere's probably an inkjet manufacturer that would be interested in getting into biotech or having their system at the heart of a biotech revolution, who's in your rolodex? :P09:28
CaptHindsightI hope that they don't cheap out copying the design I give them09:28
CaptHindsightme09:28
CaptHindsightI know them all. They are clueless when it comes to materials deposition09:29
CaptHindsightthey all want the graphics arts applications with $5/L inks that sell for $4k/L09:29
kanzuredo they recognize their relevance to industrial applications?09:30
CaptHindsightthey are money driven, if they made a POSAM it would be $100K and the fluids would be $10K/g vs $1k/g09:30
CaptHindsightthere are the greediest and most controlling types that you have met09:31
CaptHindsightthat's why the inkjet industry is so secretive09:32
kanzure"Gilead currently holds the patent rights to the SELEX technology and has licensed it to Archemix, who is using the technology to develop pharmaceutical applications for aptamers. Archemix has sublicensed this technology to NOXXON, who is using it for the development of their Spiegelmer® technology."09:32
CaptHindsightNDA's for everything09:33
kanzurehah someone patented SELEX. wonderful.... sigh.09:33
CaptHindsightkanzure: which countries advertise medical tourism and not enforce the US patent system?09:34
CaptHindsightor maybe do so less than others09:34
kanzureUS patent system is worldwide enforced through an evil organization called WIPO09:34
CaptHindsighttell that to China09:34
kanzurehttps://en.wikipedia.org/wiki/World_Intellectual_Property_Organization09:34
kanzurechina uses WIPO for their own patents09:35
CaptHindsightheh09:35
CaptHindsightwell grasshopper, you have much to discover09:35
kanzurefightaging.org was organizing a medical tourism initiative, he had picked a number of candidate countries09:35
CaptHindsightit's selective enforcement09:35
kanzurechina can turn a blindeye to some things but i get the sense that it's more related to paying off the right people, rather than china being OK with things.09:35
kanzureanyway, reason@fightaging.org would be the person to ask regarding medical tourism09:36
CaptHindsightor if your project/company is guberment funded09:36
kanzureapparently he moved to austin, texas but we've never met each other. he is trying to remain anonymous. i think i'll get him eventually.09:36
CaptHindsightbelieve me they are OK with some things09:37
CaptHindsightmost authors apply for the patent right before publishing their papers09:38
CaptHindsightwhy I often see the patent awarded <1 year after publishing09:39
CaptHindsight"hey here's what we found, loo at this" but "F-You we patented it"09:39
CaptHindsightloo/look09:40
streetythe patents on SELEX look to be over 20 years old09:40
CaptHindsighthave any open source not for profit projects ever been sued for patent infringement?09:41
kanzurewhere is mindspillage, she would have good answers09:42
CaptHindsightI'd focus on getting things to actually work09:45
CaptHindsightnegotiate later09:46
CaptHindsightit's easy to talk about something for several years without getting anything done09:47
chris_99.title http://www.bbc.co.uk/news/technology-3671199410:15
yoleauxThe DIY diabetes kit that's keeping us alive - BBC News10:15
CaptHindsightyeah #wearenotwaiting, I thought we'd be way ahead of where we are now by 200010:17
CaptHindsightI need to patent the nano-usb connector10:19
CaptHindsightwhat's a good com port for a nanoscale device to connect to a PC?10:20
CaptHindsightwhat are the most efficient ways to get data in and out of a hybrid nanoscale oligo factory?10:22
CaptHindsightsay we drop an 8-bit micro into a cell with a few K or RAM, what's the best way to communicate with it using a PC?10:23
CaptHindsightor/of10:24
kanzureprobably radio, light, stuff like that10:24
kanzurelong-term, the biologists seem to think that we will be using DNA to send messages from cells10:25
kanzurefor example, the other day in here i mentioned someone's proposal to have an array of nanopore dna sequencing devices at the human heart to read any dna messages directly from the bloodstream10:25
CaptHindsightyes, but making it practical10:26
CaptHindsightthe heart is a good central point but the cells are rushing through it pretty quickly10:26
CaptHindsightand how do you read a ton of them at once?10:26
kanzurehuge array of nanopores for sequencing10:27
kanzureif you don't capture the molecule no big deal, it will come back around eventually10:27
CaptHindsightI guess I'll have to work on the practical end10:28
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xentracCaptHindsight: one of the things the Berkeley Motes folks did was modulate a retroreflector for communication10:41
xentracso you would shine a light at a mote with, say, 1mW of light, and get back something like a 100μW signal from the mote, which was spending nW power levels moving a mirror back and forth to make and break a corner reflector10:42
kanzureanother dna synthesis proposal https://groups.google.com/d/msg/enzymaticsynthesis/8Upr8bPY-7I/R9X08u-oBwAJ10:59
fennkanzure: i guess you missed the point of FISSEQ/aptamer idea - it's not for sequencing, it's so you can do a whole lot of different stains in a single image. arbitrarily many, instead of just two or three11:13
fennIRDA for nanobot comms lol11:18
fenni knew i was saving that PDA for something11:18
CaptHindsightxentrac: recall the data rate?11:18
fennit's just a serial port11:18
kanzureFISSEQ was about sequencing, not staining :)11:19
fenn20 kbit11:20
kanzurewithout FISSEQ you can already do lots of cycles of antibody staining, imaging and washing11:20
fenn.title info.iet.unipi.it/~anastasi/papers/mswim04.pdf11:20
fennbah11:20
yoleauxfenn: Sorry, that doesn't appear to be an HTML page.11:20
fenn"Performance Measurements of Motes Sensor Networks"11:21
xentracno11:21
fennoh maybe 250 kbit11:21
kanzureif you are doing in situ sequencing with FISSEQ then you have tissue in front of a microscope, you might as well do protein expression labeling and imaging since you have the microscope there anyway. i guess you could argue "just collect all the DNA that stuck around, and sequence it later" which is nice i guess, or you could argue "nobody's got time for multiple rounds of staining and washing" and "multiple rounds is too damaging to ...11:23
kanzure... tissue" which are true things...11:23
fennkanzure the protein and RNA are not going to be in the same place11:24
kanzurehm? the aptamer is supposed to find the protein and attach to the protein.11:24
fennyes11:25
fennuh, nevermind, i thought you meant something else by "expression"11:25
kanzure"expressed proteins"11:26
kanzure(rather than "gene expression", which is apparently what lots of other people are interested in)11:26
fennCaptHindsight: "CCR reflectivity can be modulated at bit rates up to 10 kbps"11:28
fennfrom http://robotics.eecs.berkeley.edu/~pister/publications/1998/smartdust_comm_memo.pdf11:28
kanzuremarblestone did an okay writeup of a lot of potential "chips in cells" stuff11:29
fenncorner cube retroreflector is for long distance communication though, you could do a lot faster with just an LED11:30
fennassuming you have the power to run it11:31
xentracthe retroreflector thing is for avoiding the need to have the power to run it11:44
xentracI imagine you could modulate a mechanical mirror at several MHz with enough power too11:45
xentracalthough of course you can modulate many LEDs at hundreds of MHz11:45
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kanzurehttp://biology.stackexchange.com/questions/19316/first-rna-polymerase-mrna13:59
kanzure"Johnston et al. (2001) took this experiment even further: starting with a pool of slightly mutated ribozyme ligases developed in a previous SELEX experiment, they were able to generate a ribozyme polymerase. This polymerase was able to catalyze the addition of nucleotides to a growing oligonucleotide chain up to 14 bases long and based off of an RNA template. The polymerase was also quite accurate."14:01
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kanzure"RNA-catalyzed RNA polymerization: Accurate and general RNA-templated primer extension" http://fab.cba.mit.edu/classes/S62.12/docs/Bartel_RNA.pdf14:16
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kanzure.wik polynucleotide phosphorylase14:29
yoleaux"Polynucleotide Phosphorylase (PNPase) is a bifunctional enzyme with a phosphorolytic 3' to 5' exoribonuclease activity and a 3'-terminal oligonucleotide polymerase activity. That is, it dismantles the RNA chain starting at the 3' end and working toward the 5' end. It also synthesizes long, highly heteropolymeric tails in vivo." — https://en.wikipedia.org/wiki/Polynucleotide_phosphorylase14:29
kanzure"Discovered by Ochoa in 1951, the RNA-polymerization activity of PNPase was initially believed to be responsible for DNA-dependent synthesis of messenger RNA, a notion that got disproved by the late 1950s (http://www.jbc.org/content/281/15/e12.full.pdf).14:29
kanzure"14:29
kanzure"The same abbreviation (PNPase) is also used for another, otherwise unrelated enzyme, Purine nucleoside phosphorylase."14:30
kanzureugh14:30
kanzure"Polyribonucleotide phosphorylase is a double-stranded DNA-binding protein." http://www.ncbi.nlm.nih.gov/pubmed/950243314:33
kanzure"[...] The PNPase possesses two enzymatic activities, namely 3'-5' processive exoribonuclease activity and 5'-3' RNA polymerase activity"14:33
kanzure"plastid-encoded polymerase" "nucleus-encoded polymerase" "... Given that DNA and RNA polymerases both carry out template-dependent nucleotide polymerization, it might be expected that the two types of enzymes would be structurally related. However, x-ray crystallographic studies of both types of enzymes reveal that, other than containing a critical Mg2+ ion at the catalytic site, they are virtually unrelated to each other; indeed ...14:37
kanzure... template-dependent nucleotide polymerizing enzymes seem to have arisen independently twice during the early evolution of cells. One lineage led to the modern DNA Polymerases and reverse transcriptases, as well as to a few single-subunit RNA polymerases from viruses. The other lineage formed all of the modern cellular RNA polymerases."14:37
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kanzure"New Nonnucleoside Substrates for Terminal Deoxynucleotidyl Transferase: Synthesis and Dependence of Substrate Properties on Structure" (2005)16:23
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kanzurechurch writes perl :\   some of his scripts are included in various patents16:28
ebowden_Church is love, Church is life.16:28
kanzure"Genetically encoding photoswitchable click amino acids in Escherichia coli and mammalian cells" http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4051619/ (2015)16:38
kanzure"In situ formation of an azo bridge on proteins controllable by visible light" http://pubs.acs.org/doi/abs/10.1021/jacs.5b06234?journalCode=jacsat16:39
kanzure"Small molecule photoswitches could complement protein-based switches by mitigating potential interference and affording high specificity for modulation sites. However, genetic encodability and responsiveness to nonultraviolet light, two desired properties possessed by protein photoswitches, are challenging to be engineered into small molecule photoswitches. Here we developed a small molecule photoswitch that can be genetically installed ...16:40
kanzure... onto proteins in situ and controlled by visible light. A pentafluoro azobenzene-based photoswitchable click amino acid (F-PSCaa) was designed to isomerize in response to visible light. After genetic incorporation into proteins via the expansion of the genetic code, F-PSCaa reacts with a nearby cysteine within the protein generating an azo bridge in situ. The resultant bridge is switchable by visible light and allows conformation and ...16:40
kanzure... binding of CaM to be regulated by such light. This photoswitch should prove valuable in optobiology for its minimal interference, site flexibility, genetic encodability, and response to the more biocompatible visible light."16:40
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kanzureand here is one that uses spiropyran instead of azobenzene https://www.weizmann.ac.il/Organic_Chemistry/Rafal/pub/Noncovalent_Interactions_with_Proteins_Modify%20_the_Physicochemical_Properties_of_a_Molecular_Switch.pdf16:48
kanzurealthough this one does not seem to use artificial amino acids16:48
kanzure"Photosensitive GFP mutants containing an azobenzene unnatural amino acid" http://www.sciencedirect.com/science/article/pii/S0960894X1401343216:49
kanzureusing an artificial amino acid seems like a much better technique compared to using spiropyran or azobenzene in a dnazyme or ribozyme like from "Light-driven DNA nanomachine with a photoresponsive molecular engine" http://pubs.acs.org/doi/abs/10.1021/ar400308f16:50
kanzureor like from "Photoswitch nucleic acid catalytic activity by regulating topological structure with a universal supraphotoswitch" http://pubs.acs.org/doi/abs/10.1021/sb300120n16:50
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kanzure"Rewiring Multidomain Protein Switches: Transforming a Fluorescent Zn2+ Sensor into a Light-Responsive Zn2+ Binding Protein" (ligand activity modulated by photoswitching, or er, binding activity only functional under illumination, rather)16:58
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kanzure"Azobenzene photoswitching without ultraviolet light" http://2014.igem.org/wiki/images/0/0e/Technion-Israel-Azobenzene.pdf (2011) (supplementary info)17:12
kanzure"Most azobenzene-based photoswitches use UV light for photoisomerization. This can limit their application in biological systems, where UV light can trigger unwanted responses, including cellular apoptosis. We have found that substitution of all four ortho positions with methoxy groups in an amidoazobenzene derivative leads to a substantial (~35 nm) red shift of the n-π* band of the trans isomer, separating it from the cis n-π* ...17:12
kanzure... transition. This red shift makes trans-to-cis photoswitching possible using green light (530-560 nm). The cis state is thermally stable with a half-life of ~2.4 days in the dark in aqueous solution. Reverse (cis-to-trans) photoswitching can be accomplished with blue light (460 nm), so bidirectional photoswitching between thermally stable isomers is possible without using UV light at all."17:12
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CaptHindsighthhmmm no open source CGM Continuous Glucose Monitor17:29
CaptHindsightneed an open biosensor project17:33
CaptHindsightjesus , everything needs to be built17:36
CaptHindsighthas anyone actually built anything other than some software for an Rpi?17:37
kanzurelots of people use the gpio pins17:51
kanzure"A general method for regulating protein stability with light" http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906921/ (2013)18:05
kanzure"We here describe a novel genetically encoded protein domain that is degraded upon exposure to non-toxic blue light. We demonstrate that fusion proteins containing this domain are rapidly degraded in cultured cells and in zebrafish upon illumination."18:05
kanzuredegradation is a little bit overkill but i guess that's better than nothing. and it's a protein domain so that's nice..18:05
kanzure"Blue-Light Inducible Degradation (B-LID) domain"18:06
yashgarothonly works intracellularly, mediated by the proteasome18:08
kanzureoh.18:10
kanzureand the azobenzene unnatural amino acid? are you going to tell me santa claus isn't real, next?18:10
yashgarothnah that's probably fine18:11
CaptHindsightbenzos are often used in radiation/light reactive applications18:14
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kanzureyex the reason why it's useful here is because someone put it into an amino acid and an expanded genetic alphabet18:15
kanzureso a genome can specify, through genetics, that a certain amino acid in a certain protein should be responsive to light, or be light-switchable18:16
kanzurewhich is useful for an optically controlled polymerase18:16
CaptHindsightthere's a shitload of photoreactive things you can do to oligos18:16
CaptHindsightI don't think the bio people spend much time looking into what they do in industrial applications18:17
kanzureyes yesterday i pointed out a few papers where they use azobenzene and spiropyran and friends to make dnazymes and ribozymes that undergo movement in response to optical stimulation18:17
CaptHindsightthey should probably have lunch with the industrial chemists some time  :)18:17
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kanzureyeah the photopolymer/photoresin materials people seem to get involved in lots of deeply weird thngs18:22
kanzureand then there's dye stuff...18:22
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kanzurenon-covalently bound light-controlled inhibitor of a protein's catalytic activity domain http://onlinelibrary.wiley.com/doi/10.1002/anie.201307207/full (this seems to be a free-floating inhibitor)19:08
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kanzure"Methods of storing information using nucleic acids" https://patents.google.com/patent/US20150269313A1/en19:14
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kanzuresome sort of academic paper recommendation engine thing https://github.com/titipata/science_concierge19:27
kanzurefrom kording lab19:27
kanzure"sciencestein"19:27
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nildicitany thoughts on http://www.transhumanpolitics.com/ ?19:51
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kanzurewaste of time; better to build things.20:07
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nmz787damn, for half a second I read PMPase and heard it in my head as 'pimp-ase'... but then re-read and saw it was PNPase :(20:45
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nildicitkanzure, how are the political motives injected into the creation of things a waste of time tho21:01
nmz787nildicit: I don't think kanzure gets how many people out there are easily swayed by a free meal to ensue violence and/or property destruction21:06
nmz787and thus the need to educate them and get them on 'our side'21:07
nmz787(even though it seems damn obvious to us)21:07
nmz787nildicit: in general politics is basically salesmanship and communications between tribes... and being a salesman sucks21:07
nmz787I work in a tech company and was just recently told I need to sell ideas to higher-ups... because even though we're all tech folks, they need sold to because shit isn't obvious21:08
nildicitI remember an immortallife article questioning whether or not "deathism" is a meme.21:09
nildicitThose were dark times21:09
nmz787knowledge in humans doesn't seem to be able to be wide and deep for many people21:09
nildicitengineers don't like politics, I know.21:10
nildicitI've been reading into the history of the transhumanist political landscape and it's weird21:10
nildicitthings have definitely changed in the past four/five years too21:11
nildicitThe Transhumanist National Commitee was formed in response to the Zoltan Istvan's illegitimate party and campaign for instance21:13
kanzurei am going to ban you21:13
kanzurethis is an immense waste of time21:13
nildicitI'm not even trolling, kanzure21:13
nildicitYou still haven't answered my question21:14
kanzurei know. i don't care. it's still a waste of time. get the fuck out.21:14
* nildicit goes back to idling21:15
kanzureonly reason why this place is still around is because i keep murdering anyone who even hints at politicizing any of this shit; i will absolutely disembowel you and drown you in a mixture of your own blood vomit piss.21:15
kanzurethanks.21:15
nildicitNo wonder this place is pretty dead.21:16
ebowden_Not really.21:16
ebowden_Lots of technical discussion.21:17
ebowden_Oh, wait, nevermind.21:17
ebowden_Not lots.21:17
nildicitMy logs consist of more kanzure link/quoting than anything else tbh21:17
nildicitNot like that's a bad thing21:17
nildicitit's not21:17
ebowden_kanzure, did that vetinary oncologist and complete troll, Lando-SpacePimp, get banned from this channel?21:19
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kanzurethat was probably another channel21:22
ebowden_Ah, ok.21:22
ebowden_Yeah, I remember they were banned in a channel, just not which one it was.21:22
ebowden_That one is actually a scientist, just also a troll. Apparently they earned a reputation of sorts, brought Surströmming to Food Friday at vet school.21:24
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kanzurehttp://www.aptagen.com/aptamer-index/aptamer-list.aspx21:45
kanzurefenn: you shoud have argued "the wash cycles probably don't work", it's a good reason to do aptamers + sequencing rather than microscopy imaging of colors.21:56
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Th3_Princehey23:36
Th3_Princewhat should i major in if I want to go into agi23:36
chris_99hmm not sure, but you could look into computational neuroscience23:39
Th3_Princeeh23:39
Th3_Princebetween physics23:39
Th3_Princemath23:39
Th3_Princeand compsci23:39
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--- Log closed Sun Jul 17 00:00:59 2016

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